WO2017164575A1 - Nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1h-pyrrol-3-yl)-n-méthylméthanamine - Google Patents

Nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1h-pyrrol-3-yl)-n-méthylméthanamine Download PDF

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Publication number
WO2017164575A1
WO2017164575A1 PCT/KR2017/002913 KR2017002913W WO2017164575A1 WO 2017164575 A1 WO2017164575 A1 WO 2017164575A1 KR 2017002913 W KR2017002913 W KR 2017002913W WO 2017164575 A1 WO2017164575 A1 WO 2017164575A1
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WO
WIPO (PCT)
Prior art keywords
difluorophenyl
fluorophenyl
sulfonyl
acid
pyrrol
Prior art date
Application number
PCT/KR2017/002913
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English (en)
Inventor
Aeri Kim
Kwan Hyung Cho
Original Assignee
Daewoong Pharmaceutical Co.,Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020170018336A external-priority patent/KR20170113040A/ko
Priority to SI201730396T priority Critical patent/SI3433232T1/sl
Priority to PE2018001575A priority patent/PE20190169A1/es
Priority to ES17770545T priority patent/ES2811478T3/es
Priority to AU2017238917A priority patent/AU2017238917B2/en
Priority to CA3014753A priority patent/CA3014753C/fr
Priority to CN201780008658.9A priority patent/CN108602771B/zh
Priority to TNP/2018/000269A priority patent/TN2018000269A1/en
Priority to RS20201178A priority patent/RS60857B1/sr
Priority to PL17770545T priority patent/PL3433232T3/pl
Priority to MA43832A priority patent/MA43832B1/fr
Priority to MX2018009220A priority patent/MX2018009220A/es
Application filed by Daewoong Pharmaceutical Co.,Ltd. filed Critical Daewoong Pharmaceutical Co.,Ltd.
Priority to EP17770545.6A priority patent/EP3433232B1/fr
Priority to SG11201806968RA priority patent/SG11201806968RA/en
Priority to BR112018069540A priority patent/BR112018069540A2/pt
Priority to US16/073,388 priority patent/US10487053B2/en
Priority to JP2018549922A priority patent/JP6609065B2/ja
Priority to MYPI2018703343A priority patent/MY196355A/en
Priority to NZ745267A priority patent/NZ745267A/en
Publication of WO2017164575A1 publication Critical patent/WO2017164575A1/fr
Priority to CONC2018/0008834A priority patent/CO2018008834A2/es
Priority to PH12018501845A priority patent/PH12018501845A1/en
Priority to HK18113471.1A priority patent/HK1254394A1/zh
Priority to HRP20201571TT priority patent/HRP20201571T1/hr
Priority to DO2021000001A priority patent/DOP2021000001A/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/15—Fumaric acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/10—Succinic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/255—Tartaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms

Definitions

  • the present invention relates to a novel acid addition salt of l-(5-(2,4-difluorophenyl)- 1 -((3-fluorophenyl)sulfonyl) ⁇ -methoxy- 1
  • salts of certain medicines can often be important determinants of ease of preparation of medicine raw materials, solubility, stability during distribution and storage, ease of formulation and pharmacokinetic properties.
  • the production of various kinds of salts can be a means of changing the physiochemical and biological properties of the medicines without altering the chemical structure of the specific medicines.
  • the properties of many salts must be considered. For example, it can be taken into consideration depending on the environment and the situation where various factors such as ease of production, stability, solubility, and/or hygroscopicity of salt are used.
  • the present invention provides:
  • a 1 -(5-(2,4-difluorophenyl)- 1 -((3-fluorophenyl)sulfonyl)-4-methoxy- 1 H-pyrrol-3 -yl)- N-methym emanamine, which is a new active medicinal substance, is a compound represented by the following chemical formula(l), which corresponds to a 4-methoxypyrrole derivative:
  • the above 1 -(5-(2,4-difluorophenyl)- 1 -((3 -fluorophenyl)sulfonyl)-4-methoxy- 1 H- pyrrol-3-yl)-N-methyl methanamine and a pharmaceutically acceptable salt thereof can have not only a proton pump inhibitory activity, a gastric damage inhibitory activity and a defensive factor-enhancing effects, but also excellent eradication activity against Helicobacter pylori(H pylori).
  • the l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-methoxy-lH- pyrrol-3-yl)-N-memylmemanarnine and a pharmaceutically acceptable salt thereof can be effectively used for the prevention and treatment of gastrointestinal injury due to gastrointestinal track ulcer, gastritis, reflux esophagitis, or H. pylori.
  • the pharmaceutically acceptable salt of l-(5-(2,4-difluorophenyl)-l-((3- fluorophenyl)sulfonyl)-4-memoxy-lH-pyiTol-3-yl)-N-memylmemanamine can be an acid addition salt of l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-methoxy-lH-pyrrol-3- yl)-N-memylmemanamine.
  • the acid may be hydrochloric acid, succinic acid, tartaric acid, or fumaric acid.
  • the acid addition salt of l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4- memoxy-lH-pyrrol-3-yl)-N-me1hylmemanamine can be prepared by a preparation method comprising the steps of:
  • the step 1) is a step of preparing the respective solutions using a good solvent capable of completely dissolving l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-methoxy- lH-pyrrol-3-yl)-N-me&ylmemanamine and an acid, respectively, and the solvents used in dissolving l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-memoxy-lH-pyrrol-3-yl)- N-methylmethanamine and an acid may be the same or different.
  • the organic solvent may be one or more selected from the group consisting of n-hexane, ethyl acetate, butyl acetate, acetonitrile, chloroform, diethyl ether, acetone, methanol and ethanol.
  • the organic solvent in the step of preparing a l-(5-(2,4-difluorophenyl)-l-((3- fluorophenyl)sulfonyl)-4-methoxy- 1 H-pyrrol-3 -yl)-N-memylmemanamine solution, can be used as a volume (ml/g) of 1-20 times, or preferably as a volume(ml/g) of 1-10 times, relative to the weight of the l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4- memoxy-lH-pyrrol-3-yl)-N-memylmemanamine.
  • the organic solvent in the step of preparing an acid solution, can be used as a volume (ml/g) of 1-30 times, or preferably as a volume (ml/g) of 5-30 times, relative to the weight of the acid.
  • the step 2) is a step of mixing the solutions prepared in the step 1) and then stirring the mixed solutions to produce a salt in which l-(5-(2,4-difluorophenyl)-l-((3- fluorophenyl)sulfonyl)-4-methoxy-l H-pyrrol-3 -yl)-N-memylmemanamine and an acid are chemically bonded.
  • the acid in the step of mixing the prepared solutions, can be used in 0.5 to 3 equivalents or preferably in 0.5 to 2 equivalents, relative to the l-(5-(2,4-difluorophenyl)-l-((3- fluorophenyl)sulfonyl)-4-memoxy-lH-pyrrol-3-yl)-N-memylmemanamine.
  • a salt in which l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-methoxy-lH- pyrrol-3-yl)-N-memylmethanamine and an acid are bonded in a molar ratio of 1:0.5, 1:1, 1:1.5, or 1 :2 can be produced.
  • the step of stirring the mixed solutions can be carried out at a temperature of 24 ° C to 28 ° C for 30 minutes to 4 hours. At this time, the stirring speed may be in the range of 50 rpm to 300 rpm. Within this range, salts with high yield and high purity can be produced.
  • the acid addition salt of l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4- methoxy-lH-pyrrol-3-yl)-N-memylme1hanamine prepared by the above preparation method can be recovered from the solution by the vacuum filtration method. If necessary, the recovered acid addition salt was washed and dried under vacuum to obtain an acid addition salt with high purity.
  • the reaction conditions such as the ratio of solvent, the temperature range, the process time, and the like described in the above preparation method can be adjusted depending on the selected solvent.
  • the present invention provides a pharmaceutical composition for the prevention and treatment of gastrointestinal injury due to gastrointestinal tract ulcer, gastritis, reflux esophagitis, or H. pylori, comprising one or more acid addition salts selected from the group consisting of hydrochloride, succinate, tartrate and fumarate of l-(5-(2,4-difluorophenyl)- l-((3-fluorophenyl)sulfonyl)-4-methoxy-lH-pyrrol-3-yl)-N-me1hylmethanam
  • Such pharmaceutical composition may include pharmaceutically acceptable carriers that are commonly used.
  • the carrier be one that is usually used at the time of formulation, and it includes lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil and the like, but are not limited thereto.
  • the pharmaceutical composition may further include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.
  • the pharmaceutical composition may be administered orally, or administered parenterally, including intravenous, intramuscular, intraperitoneal, subcutaneous and transdermal, routes of administration.
  • the pharmaceutical composition may be administered in a therapeutically effective amount, for example, in an effective amount ranging about 0.001 mg kg to about 100 mg/kg per day.
  • the dosage may vary depending on formulation method, administration method, patient's age, body weight, sexually transmitted infection, diet, administration time, administration route, excretion rate or susceptibility.
  • the pharmaceutical composition can be formulated by the method that can be performed easily by those in the art by using a pharmaceutically acceptable carrier and/or excipient in the form of unit dose or in multi-dose container.
  • the formulation can be used without limitation as long as it is in any form suitable for pharmaceutical preparations including oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups or aerosols, external preparations such as ointments or creams, suppositories and sterilized injection solutions.
  • a dispersing agent or a stabilizer can be further included.
  • the acid addition salts of l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4- memoxy-lH-pyrrol-3-yl)-N-memylmemanamine according to the present invention have high solubility in water and excellent stability under moisture-proof conditions and high-humidity exposure conditions, and thus can be pharmaceutically used.
  • Acetic anhydride (1731.2 ml) and triethylarnine (577.1 ml) were added to 2-(2,4- difluorophenyl)-2-((3-me1hoxy-2-(memoxycarbonyl)-3-oxoprop-l-en-l-yl)amino)acetic acid (190.0 g, 577.1 mmol) prepared in the step 1-1.
  • the reaction mixture was refluxed at 140 ° C for 30 minutes and then cooled to 0 ° C .
  • ice water (577.1 ml) was added at 0 ° C , stirred at room temperature for 1 hours and then extracted with ethyl acetate.
  • the obtained extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
  • the resulting compound was filtered using silica gel to remove solids, and then concentrated under reduced pressure.
  • Methyl 5-(2,4-difluorophenyl)-4-methoxy-lH-pyrrol-3-carboxylate (18.0 g, 67.4 mmol) prepared in the step 1-3 was dissolved in dimethylformamide (335.0 ml).
  • sodium hydride (60%, dispersion in liquid paraffin) (4.0 g, 101.0 mmol) was added at room temperature and the mixture was stirred at room temperature for 10 minutes.
  • 3-fluorobenzenesulfonyl chloride 13.37 ml, 101.0 mmol was added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture and extracted with ethyl acetate.
  • Step 1-6 Preparation of l-(5-(2,4-difluorophenyl)-4-methoxy-l-((3- fluorophenyl)sulfonyl)-lH ⁇ yrrol-3-yl)-N-methylmethanamine
  • Example 1 Preparation of l-(5-(2, -difluorophenyl)-l-((3-fluorophenyl)sulfonyl)- -metho -lH-pyrrol-3-yl)-N-methylmethanamine hydrochloride
  • Example 2 Preparation of l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)- 4-metho -lH-pyrrol-3-yl)-N-methylmethanamine succinate
  • Test Example 1 Inhibitory effects on proton pump (H+/K+-ATPase) activity
  • Gastric vesicles were prepared from a hog stomach according to a known method (Edd C. Rabon et al., Preparation of Gastric Ff ⁇ K ⁇ ATPase., Methods in enzymology, vol.157 Academic Press fnc.,(1988), pp.649-654).
  • the protein contents of gastric vesicles thus prepared were quantitatively measured with Bicinchoninic Acid (BCA) kit (Thermo).
  • BCA Bicinchoninic Acid
  • the concentration (IC 50 ) that inhibits FT7K + -ATPase activity by 50% was calculated from each % inhibition value of the compounds using Logistic 4-parameter function of Sigmaplot 8.0 program.
  • IC 50 concentration that inhibits FT7K + -ATPase activity by 50%
  • Logistic 4-parameter function of Sigmaplot 8.0 program As a result, l-(5-(2,4-difluorophenyl)-l-((3-fluorophenyl)sulfonyl)-4-melhoxy-lH- pyrrol-3-yl)-N-methylmethanamine hydrochloride prepared in Example 1 exhibited an IC50 value of 0.024 uM.
  • an acid addition salt of l-(5-(2,4-difluorophenyl)-l-((3- fluorophenyl)sulfonyl)-4-methoxy-lH-pyrrol-3-yl)-N-methylmethanam had excellent proton pump inhibitory activity and thus can be used for a pharmaceutical composition for the prevention and treatment of gastrointestinal injury due to gastrointestinal tract ulcer, gastritis, reflux esophagitis, or H. pylori.
  • the hygroscopicity test was carried out for the acid addition salts prepared in the above Examples.
  • 40 mg of the salts of the Examples were tightly sealed and stored in each glass desiccator containing a saturated aqueous solution of several salts for at least two days under the condition of constant relative humidity as shown in Table 1 below. Subsequently, the result of measurement of weight change for each of these salts showed that weight change due to moisture was not observed. Accordingly, it could be seen that the acid addition salts prepared in the Examples did not have hygroscopicity.
  • the stability test was carried out for the acid addition salts prepared in the Examples to evaluate the degree to which impurities were formed during storage under severe conditions (moisture-proof condition and high-humidity exposure condition).
  • the results of the stability test under the moisture-proof condition were shown in Table 2 below, and the results of the stability test under the high-humidity exposure condition were shown in Table 3 below.
  • vials containing 10 mg of each sample which was precisely weighed and taken were prepared in the planned quantity, and they were stored by dividing into the moisture-proof condition (60 ° C and less than 10% relative humidity) and under the high- humidity exposure condition (60 ° C and 95% relative humidity). However, under the high- humidity exposure condition, a stopper of the vial was not used to keep so that the sample is in sufficient contact with a moisture in the air.
  • the solubility test in water was carried out for the acid addition salts prepared in the Examples, and the results were shown in Table 4 below.
  • a sample of less than 10 mg was first precisely weighed and taken, and placed into a vial, to which 50 ⁇ of deionized water was added, shaking for 30 seconds and ultrasonic shaking for 1 minute were carried out, and these processes were repeated several times.
  • the water solubility was calculated by measuring the amount of water used to dissolve all the samples.
  • Examples had a water solubility of 10 times or more as compared with that of the free base prepared in Preparation Example.
  • the acid addition salts prepared in the Examples showed high solubility in the order of hydrochloride, succinate, tartrate and fumarate.

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  • Organic Chemistry (AREA)
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Abstract

La présente invention décrit un nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1H-pyrrol-3-yl)-N-méthylméthanamine. Le sel d'addition d'acide ci-dessus décrit présente non seulement une excellente activité inhibitrice de la pompe à protons, une excellente activité inhibitrice des dégâts gastriques et un excellent effet de renforcement des facteurs de défense, mais également une excellente activité d'éradication de H. pylori et il peut donc être efficacement utilisé pour la prévention et le traitement des lésions gastro-intestinales dues à l'ulcère du tractus gastro-intestinal, à la gastrite, au reflux œsophagien, ou à H. pylori.
PCT/KR2017/002913 2016-03-25 2017-03-17 Nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1h-pyrrol-3-yl)-n-méthylméthanamine WO2017164575A1 (fr)

Priority Applications (23)

Application Number Priority Date Filing Date Title
NZ745267A NZ745267A (en) 2016-03-25 2017-03-17 Novel acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1h-pyrrol-3-yl)-n- methylmethanamine
SG11201806968RA SG11201806968RA (en) 2016-03-25 2017-03-17 Novel acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1h-pyrrol-3-yl)-n- methylmethanamine
EP17770545.6A EP3433232B1 (fr) 2016-03-25 2017-03-17 Nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1h-pyrrol-3-yl)-n-méthylméthanamine
AU2017238917A AU2017238917B2 (en) 2016-03-25 2017-03-17 Novel acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N- methylmethanamine
PE2018001575A PE20190169A1 (es) 2016-03-25 2017-03-17 Nueva sal de adicion de acido de 1-(5-(2,4-difluorfenil)-1-(3-fluorfenil)sulfonil)-4-metoxi-1h-pirrol-3-il)-n-metilmetanamina
CN201780008658.9A CN108602771B (zh) 2016-03-25 2017-03-17 化合物的酸加成盐
TNP/2018/000269A TN2018000269A1 (en) 2016-03-25 2017-03-17 Novel acid addition salt of 1-(5-(2.4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1 h-pyrrol-3-yl)-n- methylmethanamine.
BR112018069540A BR112018069540A2 (pt) 2016-03-25 2017-03-17 sal de adição de ácido de 1?(5?(2,4?difluorfenil)?1?((3?fluorfenil)sulfonil)?4?metóxi?1h?pirrol?3?il)?n?metilmetanoamina inédito
PL17770545T PL3433232T3 (pl) 2016-03-25 2017-03-17 Nowa sól addycyjna 1-(5-(2,4-difluorofenylo)-1-((3-fluorofenylo)sulfonylo)-4-metoksy-1H-pirol-3-ilo)-N-metylometanoaminy z kwasem
MA43832A MA43832B1 (fr) 2016-03-25 2017-03-17 Nouveau sel d'addition d'acide de 1-(5-(2,4-difluorophényl)-1-((3-fluorophényl)sulfonyl)-4-méthoxy-1h-pyrrol-3-yl)-n-méthylméthanamine
MX2018009220A MX2018009220A (es) 2016-03-25 2017-03-17 Nueva sal de adicion acida de 1-(5-(2,4-difluorfenil)-1-((3-fluorf enil)sulfonil)-4-metoxi-1h-pirrol-3-il)-n-metilmetanamina.
SI201730396T SI3433232T1 (sl) 2016-03-25 2017-03-17 Nova kislinska dodatna sol 1-(5-(2,4-difluorofenil)-1-((3-fluorofenil)sulfonil)-4-metoksi-1H-pirol- 3-IL)-N-metilmetanamina
ES17770545T ES2811478T3 (es) 2016-03-25 2017-03-17 Nueva sal de adición de ácido de 1-(5-(2,4-difluorofenil)-1-((3-fluorofenil)sulfonil)-4-metoxi-1H-pirrol-3-il)-N-metilmetanamina
CA3014753A CA3014753C (fr) 2016-03-25 2017-03-17 Sel d'addition acide de 1-(5-(2,4-difluorophenyl)((3-fluorophenyle)sulfonyle)-4-methoxy-1h-pyrr ol-3-yl) methylmethanamine
RS20201178A RS60857B1 (sr) 2016-03-25 2017-03-17 Nova kisela adiciona so 1-(5-(2,4-difluorofenil)-1-((3-fluorofenil)sulfonil)-4-metoksi-1h-pirol-3-il)-n- metilmetanamina
US16/073,388 US10487053B2 (en) 2016-03-25 2017-03-17 Acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine
JP2018549922A JP6609065B2 (ja) 2016-03-25 2017-03-17 １−（５−（２，４−ジフルオロフェニル）−１−（（３−フルオロフェニル）スルホニル）−４−メトキシ−１ｈ−ピロール−３−イル）−ｎ−メチルメタンアミンの新規な酸付加塩
MYPI2018703343A MY196355A (en) 2016-03-25 2017-03-17 Novel acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1h-pyrrol-3-yl)-n- methylmethanamine
CONC2018/0008834A CO2018008834A2 (es) 2016-03-25 2018-08-24 Nueva sal de adición de ácido de 1–(5–(2,4–difluorfenil)–1–((3–fluorfenil)sulfonil)–4–metoxi–1h–pirrol–3–il)–n–metilmetanamina
PH12018501845A PH12018501845A1 (en) 2016-03-25 2018-08-30 Novel acid addition salt of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1h-pyrrol-3-yl)-n- methylmethanamine
HK18113471.1A HK1254394A1 (zh) 2016-03-25 2018-10-19 1-(5-(2，4-二氟苯基)-1-((3-氟苯基)磺酰基)-4-甲氧基-1h-吡咯-3-基)-n-甲基甲胺的新酸加成鹽
HRP20201571TT HRP20201571T1 (hr) 2016-03-25 2020-10-04 Nova kisela adicijska sol 1-(5-(2,4-difluorofenil)-1-((3-fluorofenil)sulfonil)-4-metoksi-1h-pirol-3-il)-n- metilmetanamina
DO2021000001A DOP2021000001A (es) 2016-03-25 2021-01-06 Nueva sal de adición de ácido de 1–(5–(2,4–difluorfenil)–1–((3–fluorfenil)sulfonil)–4–metoxi–1h–pirrol–3–il)–n–metilmetanamina

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2016-0036081 2016-03-25
KR20160036081 2016-03-25
KR10-2017-0018336 2017-02-09
KR1020170018336A KR20170113040A (ko) 2016-03-25 2017-02-09 1-(5-(2,4-다이플루오로페닐)-1-((3-플루오로페닐)술포닐)-4-메톡시-1h-피롤-3-일)-n-메틸메탄아민의 신규한 산부가염

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WO2017164575A1 true WO2017164575A1 (fr) 2017-09-28

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